Neuroethics guidance documents: principles, analysis, and implementation strategies

Abstract Innovations in neurotechnologies have ignited conversations about ethics around the world, with implications for researchers, policymakers, and the private sector. The human rights impacts of neurotechnologies have drawn the attention of United Nations bodies; nearly 40 states are tasked with implementing the Organization for Economic Co-operation and Development’s principles for responsible innovation in neurotechnology; and the United States is considering placing export controls on brain-computer interfaces. Against this backdrop, we offer the first review and analysis of neuroethics guidance documents recently issued by prominent government, private, and academic groups, focusing on commonalities and divergences in articulated goals; envisioned roles and responsibilities of different stakeholder groups; and the suggested role of the public. Drawing on lessons from the governance of other emerging technologies, we suggest implementation and evaluation strategies to guide practitioners and policymakers in operationalizing these ethical norms in research, business, and policy settings.


I. INTRODUCTION
Neurotechnologies are poised to drive significant changes to areas from healthcare to human rights.These technologies could transform mobility assistance to those with paralysis, offer interventions for mental health, and drive economic growth.They could also pose new safety and privacy threats, challenge human autonomy, and exacerbate inequality.While emerging technologies that promise broad societal changes are not new, neurotechnologies' association with the brain creates unique concerns, and scholars and policy bodies have identified significant ethical and policy issues surrounding neurotechnologies. 1 As such, neurotechnologies have sparked conversations about ethical impacts in a broad range of organizations.For example, the United Nations has recently directed focus toward human rights implications of neurotechnologies, 2 and the United Nations Educational, Scientific and Cultural Organization is considering the development of a standard-setting instrument on the ethics of neurotechnology. 3Nearly 40 national governments have committed to implement the Organization for Economic Co-operation and Development's nine principles for responsible innovation in neurotechnologies, which calls for both public and private sector action. 4Illustrating the prominence of national security concerns, the United States is currently considering placing export controls on brain-computer interfaces. 5These nascent discussions and actions have both immediate and long-term implications for researchers, policymakers, the private sector, and society.
In response to these conversations, national and international bodies, academic groups, and technical societies have issued a variety of guidance documents, principles, and frameworks to shape the development and use of neurotechnologies (Table 1).Stakeholders attempting to translate these recommendations into actionable steps need a central access point to this guidance as well as clear strategies for implementation.
In this paper we offer the first review and analysis of existing neuroethics guidance documents (Table 1) recently issued by prominent government, private, and academic groups and offer a deeper discussion of potential implementation strategies.We first examine commonalities and divergences in recent neuroethics guidance documents, focusing on articulated goals, underlying governance frameworks, and the suggested roles and responsibilities of various stakeholders.Drawing on this analysis and lessons from other emerging technologies, we suggest implementation tools and strategies to guide regulatory bodies, policymakers, academia, and the private sector.

II.A. Articulated Goals, Gaps, and Stakeholders
Guidance documents often justify their development by describing the moral significance and scientific excitement associated with understanding the brain.Brain technologies draw attention due to their current and anticipated potential to enable new medical advances, increase productivity and drive economic growth, and advance national security.
While some documents6 offer recommendations for a broad set of stakeholders, others target more specific audiences such as clinicians and physicians, 7 specific

Table 1.
We include English-language documents originally published before February 2022 that provide ethics principles, frameworks, guidelines, and policy strategies for neurotechnology.We include documents written by government or intergovernmental entities as well as documents written by nonprofit, advocacy, and professional organizations, but exclude documents whose authors do not speak as representatives of an organization governmental or intergovernmental bodies,8 industry, 9 or the scientific community. 10n this sense, documents are presented with a trade-off: those that more narrowly target specific concerns and stakeholder groups often provide the most concrete and actionable recommendations, while those that are broader in scope may lead to less direct action but could be more effective in influencing narratives and agendas. 11ach document articulates benefiting the public as a core goal, but documents describe different strategies for achieving this.Some aim to benefit the public indirectly by advancing or protecting the scientific enterprise and field of medicine, 12 a strategy particularly common in documents targeted toward scientists and clinicians.Others describe principles intended to benefit the public more directly by protecting them from potential harms. 13

II.B. Governance Frameworks and Underlying Assumptions
Many documents 14 derive principles and recommendations from Responsible Research and Innovation (RRI), a science policy framework popularized in the E.U. that emphasizes that science and technology are socially, ethically, and politically interconnected, and that science policy must engage with and be built by a community to serve the community.
Other documents 15 derive principles and recommendations from field-specific ethical structures.For example, documents targeted to clinicians often adapt medical ethics frameworks such as the Belmont Report and Beauchamps and Childress' principles of biomedical ethics, while documents targeted to researchers are often derived from bioethics frameworks, placing emphasis on ethics training in education and institutions such as institutional review boards (IRBs).
Two other ideas are commonly used to derive ethical principles.First, documents 16 commonly reference brain exceptionalism, 17 the notion that the brain is a uniquely morally salient organ.Second, some documents we analyzed 18 stress the existence of (and importance of respecting) cultural considerations.These ideas may come into tension with each other: beliefs about agency, autonomy, identity, and the significance of the brain may differ between Western and non-Western cultures. 19While documents pointed to the importance of cultural awareness and inclusivity, they offer few directives.This tension echoes debates surrounding human rights, where calls for 'universal' values pointing to the pitfalls of ethical relativism come in conflict with a desire to respect diverse cultural norms. 20

II.C. Key Topics and Patterns
Key themes, topics, and principles described by documents tend to fall into two major categories.First, documents discuss novel ethical concerns raised by neurotechnologies: safety and privacy; equity and justice; and issues of agency, autonomy, and identity (Table 2).Second, documents discuss procedural and governance concerns that are uniquely or particularly relevant for neurotechnologies (Table 3).

Ethical Concerns
Highlighted safety concerns include both physical and nonphysical harms related to technologies that interact with-and could modify-the brain in unprecedented ways.power in data brokers.However, fewer documents22 describe major trade-offs inherent to strengthening privacy protections, such as the difficulty of obtaining meaningful informed consent for data collection, cultural variations in notions of privacy, and the costs that restricting data sharing impose on scientific research.

Governance and Procedural Concerns
Governance issues highlighted include innovation and regulation policy (such as the need to smooth regulatory pathways for novel therapies), gaps in existing governance structures (for example, gaps in how consumer and medical devices are regulated), and the importance of inter-stakeholder dialog and coordination.Most documents focus on market-based approaches to innovation and governance; a minority of documents23 explicitly discuss limitations and constraints of private stakeholders' responsibility to create shareholder value.
To avoid harmful applications of neurotechnologies, governance-body-oriented documents often focus on horizon scanning capabilities,24 while developer-oriented documents often focus on precautionary principles and the need to avoid 'sensitive' or 'malign' applications (e.g., manipulative marketing, coercion, or military/dual use). 25ecommendations frequently cover procedural issues related to neuroscience research and clinical practice.Several documents 26 articulate a need for neuroethics to be embedded in research and medicine.Documents with other orientations tend to focus more on field-specific oversight mechanisms, such as institutional review boards (IRBs) in clinical trials.Citing the net-societal-benefits of research progress, documents often recommend strategies to accelerate neuroscience research (for example, by enhancing access to shared data and computational resources).Documents also allude to specific ethical issues arising in research and medicine, such as regard for brain donors and non-human animals in research.Finally, in acknowledgement of concerns about hype and hyperbole, some documents with clinical orientations 27 caution that clinicians should apply a high standard of evidence to novel neurotherapies.

II.D. Public Participation and Dialog
Guidance documents consistently call for increased communication and dialog with the public.This call is typically framed either as filling a void that might otherwise stimulate misinformation or hyperbole, 28 or as a more positively-framed attempt to promote civic engagement and dialog. 29Many documents 30 eschew one-way public education efforts in favor of two-way public dialogue, echoing scholarly criticism of the information deficit model of science communication. 31ocuments ascribe a variety of potential benefits to this two-way public dialogue.One is cultivating public trust in science, an objective alternately framed as respecting public opinion and as avoiding 'triggering' public concerns in a way that might reduce public support for neurotechnologies.A second commonly-described benefit of public dialog is building the capacity of the public to engage in debate, shape neurotechnologies' development, and construct better incentive structures for technology developers.This latter theme is more consistent with RRI frameworks, which call for engagement as a route to meaningful incorporation of public sentiment into policymaking rather than as an outreach exercise alone. 32Of particular emphasis is the importance of building capacity to provide informed consent for medical procedures, and the value of neuroscience education for lawyers and judges.

II.E. Suggested Stakeholder Roles and Responsibilities
One fundamental difference between documents is in their relative emphases on individual responsibility and the need for new incentive and regulatory structures.Documents at one end of this spectrum33 portray groups such as neuroscientists and industry as having a powerful self-interest to act responsibly and preserve public trust.Documents closer to the other end of this spectrum34 do not place sole ethical responsibility on technology developers, instead calling for governments and other stakeholders to develop incentive structures to encourage prosocial behavior.

Clinicians
Physicians are frequently described as having the responsibility to follow their field's traditional principles for responsible practice and medical ethics.Clinically-oriented documents often 35 provide physicians with a wide degree of independence and judgment (though others36 note the importance in developing clinical consensus).

Researchers
Researchers are frequently called on to proactively consider and communicate potential implications of scientific advances.The scientific enterprise in particular is often called upon to improve and meaningfully incorporate ethics in training and the conduct of research, while professional groups are sometimes called on to develop technical standards that can incentivize prosocial outcomes.

Government
Governments are often described as representatives of the public,37 charged with advancing the interests of underrepresented populations and the natural environment.This results in governments often being tasked with broad goals intended to mitigate the constraints and limitations of other stakeholders.For example, governments are frequently assigned responsibility for addressing equity and justice concerns; wrestling with market forces to steer scientific progress toward societal needs; creating structures for inter-stakeholder dialog and public participation; and implementing horizonscanning efforts.These vague responsibilities described by broadly-targeted documents contrast with the more concrete but narrowly-scoped recommendations of documents that aim to provide recommendations to specific bodies of governments, which tend to emphasize building technical capacity in government to anticipate ethical concerns; government-led ethical reviews; emphasis on ethics in research funding; and building inter-government and inter-stakeholder dialogs.

Funding Bodies
Government funding organizations in particular are often called on to take an anticipatory approach to funding research.Funding agencies are often described38 as capable of building incentive structures that steer research trajectories toward societal needs, and are commonly called on to fund ethics training for scientists and integration of ethicists into technical research teams.Research in neuroethics (e.g., on the meaningfulness of consent when therapies may produce personality change) is also cited as an important funding priority.
Many documents39 note that consultations and collaborations with ethicists could reduce the need for scientists and developers to have the experience required to anticipate potential ethical implications of their work, a setup that funding agencies are often called on to support.It is also important that scientists working in the private sector have access to consultations and collaboration with ethicists; many companies may invest in legal/compliance groups but lack ethics resources.

Media and Public Communicators
One of the most consistent calls 40 is for stakeholders (e.g., industry, universities, and the media) to perform responsible public communication that avoids hyperbole.Here, too, the field as a whole is often described as having a vested interest in preserving public trust.When more specific recommendations are made, they typically involve the creation of independent or multi-stakeholder bodies responsible for fact-checking and moderating hype.societies or licensing authorities can be influential in setting the legal standards of care that inform malpractice case outcomes or licensing decisions, providing these actors with a powerful lever for promoting more ethical uses of new therapeutics.Here, setting standards of care, as well as guidance on informed consent, will be influential in how physicians describe and apply new neurotechnologies.For example, a recent consensus workshop recommends that neuroradiologists who offer inaccurate or biased expert testimony be subject to sanction by their professional society. 42

III.B. Implementation Strategies for Industry
Guidance documents nearly universally call for corporate responsibility and stewardship, though robust public and civil society oversight, engagement, and incentive structures (including liability) will likely improve the effectiveness of private sector strategies.Increasingly-popular Environmental, Social, and Governance (ESG) investing strategies may provide one such mechanism; ESG indicators accounting for neuroethical principles could provide for improved regulatory monitoring and more responsible investment.Increased attention to ethics in technical standard-setting, private investment and research funding, industry codes of conduct, and liability schemes may further incentivize corporate stewardship.'Ethical licensing', 43 in which patent holders place ethics-based restrictions on how licensees can apply new technologies, provides developers a lever to encourage adherence to neuroethical principles.national data governance laws that place rules on storing data locally or transferring data across borders. 45

III.D. Implementation Strategies for Regulatory Bodies
Government bodies often suffer from incomplete or overlapping authority, conflicts between the economic and social interests of innovation, and difficulty in implementing vague principles.However, public bodies also have many regulatory and funding tools at their disposal.To translate ethical principles into action, governments and regulatory bodies can: 1. Treat Brain Data with Special Import Many companies derive significant value from collecting and processing users' personal data 46 ; because the commercially valuable inferences made from this data may go significantly beyond what users expect, traditional informed consent procedures may be inadequate. 47Brain data merit special consideration by regulators.Increased antitrust enforcement and global scrutiny of organizations that collect large amounts of brain data may protect consumers and prevent undesired accumulation of power.Given the sensitive nature of brain data, its use by state and law enforcement also raises concerns about rule of law norms such as due process, governmental search and seizure, nondiscrimination, and freedom of thought. 48

Use Healthcare Provision to Encourage Equitable Access
Guidance documents often task governments with ensuring that new therapeutics (or enhancements) do not exacerbate inequality.Governments can increase access equity by utilizing bodies that make reimbursement decisions, such as the UK's National Institute for Health and Care Excellence (NICE) or the U.S.'s Medicare and Medicaid, to consider equity when making coverage decisions.While governments can also direct insurers to cover certain new technologies, inequities in insurance coverage mean that countries with universal healthcare schemes have more powerful mechanisms to promote access equity.

Strengthen Post-Market Surveillance to Bridge the Consumer/Medical Regulatory
Divide Gaps in the regulatory frameworks used for neurotechnologies marketed for consumer and medical use can allow new products to avoid appropriate regulation and increase the importance of coordination between regulatory bodies. 49Post-market surveillance 50 may provide regulators with increased flexibility to address the unique challenges of nominally consumer-oriented neurotechnology products, though this should not serve as a replacement for appropriate premarket safety evaluations.

Consider More Responsive or Novel Governance Strategies
For example, providing regulatory agencies with broader mandates, promoting interagency cooperation, or utilizing sunset provisions for rules may improve responsiveness to broader social interests.Flexible regulatory strategies such as co-regulatory schemes (in which regulators work closely with regulated parties rather than imposing top-down regulation) have been used in nanotechnology and artificial intelligence to guide innovation toward more responsible outcomes. 51However, these more flexible approaches often require additional accountability and transparency mechanisms to ensure that private interests do not consume regulatory policy.Market forces may also reduce economic incentives for industry to develop therapies for diseases that are particularly rare or otherwise unprofitable, deficiencies that governments can address through public funding or specialized regulatory pathways such as the U.S. FDA's Breakthrough Devices Program.

Utilize International and Scientific Advisory Bodies for Horizon Scanning, Technology
Assessment, and International Coordination For example, the U.S. National Academies, the UK Royal Society, and the Chinese Academy of Sciences have co-organized international workshops that convened crossjurisdictional stakeholders to discuss policy implications of heritable human genome editing, 52 and the World Health Organization has developed a menu of policy options to inform national and international regulation of this technology. 53Attempts to move neuroethics guidance from principles to practice could similarly benefit from these types of international and cross-jurisdictional cooperation, alongside the existing efforts of the OECD, UNESCO, and others.

Build and Update International Agreements, But Not to the Exclusion of National and
Regional Governance While emerging technologies rarely prompt novel, binding treaties, calls for new and updated human rights in response to neurotechnology developments echo successful (but nonbinding) international instruments such as UNESCO's 2005 Universal Declaration on Bioethics and Human Rights. 54Although these international human rights efforts have important narrative and agenda-setting value, national and regional implementation may be more responsive to local cultural considerations and could have greater long-term legitimacy.Customary international law may offer other routes for developing new legal norms without novel treaties, though this process can take decades.For example, the OECD's 2019 instrument 55 and UNESCO's 2021 report 56 may provide norms which future international courts could invoke as custom.

III.D. Implementation Strategies for Public Engagement
Guidance documents almost universally call for increased public outreach and engagement, and some documents suggest concrete strategies. 57However, the historical attempts at public engagement about emerging technologies point to both political and financial challenges. 58any guidance documents also call for increasing the quality of public discourse about neurotechnology by improving accuracy and reducing hyperbole.Consumer protection agencies such as the US Federal Trade Commission could strengthen incentives for accurate communication, and lawmakers could consider requiring disclosure of information pertinent to neuroethical norms, steps that could raise the potential for reputational and market consequences for noncompliance with ethical principles (even if no direct legal consequences would result). 59Partnerships between researchers and industry that provide the public with trustworthy information could serve the longterm interests of both the public and the field, but care should be taken to meaningfully represent diverse constituents (such as patient groups) and avoid real or perceived capture by industry actors that could erode public trust and moral authority.

III.E. Evaluating Impact
One route to impact for guidance documents is to make specific, actionable, and politically acceptable recommendations.These specific recommendations provide a clear means for evaluation: are committees, working groups, reports, or rulemaking processes created when called for?Are public engagement events held-and results used to inform policy-when recommended, or is the desire for public participation left as a vague aspiration?Various calls for public engagement prior to the implementation of heritable human genome editing, for example, have yet to yield meaningful policy inputs. 60ven when they do not drive direct action, however, guidance documents can achieve impact indirectly by changing values, narratives, and agendas.Though harder to measure, intergovernmental bodies such as the OECD, UNESCO, and Council of Europe have increasingly made explicit references to rights and principles relevant to emerging neurotechnologies 61 ; the Chilean legislature recently amended their constitution to add 'neuro rights' provisions in response to advocacy by the newly formed NeuroRights Foundation. 62egardless of the route to impact, early signs of the impact of guidance documents may include citations in academic and grey literature or legal documents such as court briefs, judicial opinions, or official transcripts of legislative hearings.Documents cited in technical standards or insurance underwriting are likely to have a larger and more direct impact in technology development, as standards and insurance often serve as a key form of soft law for emerging technologies. 63For example, insurers have become quasi-regulators of technologies such as artificial intelligence and nanotechnology as they choose what risk they are willing to absorb and what technological applications they will underwrite. 64

IV. CONCLUSION
While emerging neurotechnologies promise significant medical and economic benefits, they also pose novel ethical concerns, from new safety and privacy risks to novel conceptions of human agency and identity.While articulating these concerns is an important first step, it is critical that ethical principles are matched by action.Stakeholders are each constrained by unique obstacles: no governance strategy provides a silver bullet, and successful governance strategies will likely require adaptation over time.
In the face of these challenges, this article presents a set of governance tools to help diverse stakeholders positively shape the impact of neurotechnologies.By beginning to take steps toward governance now, neuroscientists, developers, clinicians, and governance agencies can help translate the ethical principles articulated by guidance documents into positive societal impact.

Table 2 .
Key ethics concerns described in guidance documentsMatching these individual risks to safety and privacy are societal risks concerning equity and justice.Equity concerns focus on cultural biases in research as well as the equitable distribution of both benefits (e.g., novel therapies and enhancements) and harms (e.g., clinical trial subjects).Documents also warn of stigma created when the apparent objectivity of neuroscience research is used to define 'normality' and discrimination that could result from the unquestioned use of neuroscience in the courtroom.Privacy is frequently described as having particular importance for brain data, 21 with documents citing reidentification risks, unexpected future uses, and concentration of 21 Nuffield Council on Bioethics; CeReB: The Center for Responsible Brainwave Technology; U.S. Presidential Commission for the Study of Bioethical Issues; U.S. Presidential Commission for the Study of Bioethical Issues; R. Yuste et al.; K.S. Rommelfanger; H.T. Greely et al.; NIH Advisory Committee to the Director (ACD) Working Group on BRAIN 2.0 Neuroethics Subgroup (BNS); The Japanese Neuroscience Society; Organization for Economic Cooperation and Development (OECD); International Bioethics Committee of UNESCO (IBC); M. Ienca et al., supra notes 6-10, 13.

Table 3 .
Key governance concerns described in guidance documents